Epidemiological studies have demonstrated that increased cancer risk is associated with obesity, but the underlying mechanism remains poorly understood. We have recently developed a Drosophila model of obesity; raising Drosophila on a diet high in carbohydrates led to metabolic dysfunction including hyperglycemia, insulin-resistance and accumulation of fat. Feeding a high dietary sucrose to Ras/Src co- activated Drosophila cancer model developed aggressive tumor with emergent metastasis in a diet-dependent manner. The goal of this Application is to further utilize Drosophila as a useful in situ model to explore mechanistic link between diet-induced obesity and tumor progression. PUBLIC HEALTH RELEVANCE: Epidemiological studies have long shown that obesity and other metabolic dysfunctions increase the risk and severity of tumor progression. In this Application we use fruit flies to explore the mechanisms by which high dietary sugar enhances tumorigenesis.